Nucleic acids encoding anti-IL-6 antibodies of defined epitopic specificity

• US 20130017575A1
• Filed: 11/17/2011
• Published: 01/17/2013
• Est. Priority Date: 05/21/2007
• Status: Abandoned Application

• Current Assignee: H. Lundbeck A/S (Lundbeck Foundation)
• Original Assignee: H. Lundbeck A/S (Lundbeck Foundation)
• Inventors: Garcia-Martinez, Leon, Jensen, Anne Elisabeth Carvalho, Olson, Katie, Dutzar, Ben, Ojala, Ethan, Kovacevich, Brian, Latham, John, Smith, Jeffrey T.L.
• Application Number:
  US13/298,407
• Publication Number:
  US 20130017575A1
• Time in Patent Office: Days
• US Class Current: 435/69.6
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/248 IL-6
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C12N 15/81 for yeasts
• CPC Class Codes: C12N 9/60 from yeast
• CPC Class Codes: C12N 9/64 derived from animal tissue
• CPC Class Codes: C12P 21/02 having a known sequence of two or more amino acids, e.g. glutathione

Abstract

The invention relates to nucleic acids encoding antibody or antibody fragments that specifically binds to an epitope on an intact human IL-6 polypeptide, which epitope when ascertained by epitopic mapping includes one or more residues comprised in each of the following IL-6 fragments (i) a fragment consisting of amino acid residues 37-51 of human Il-6, (ii) a fragment consisting of amino acid residues 70-84 of human Il-6, (iii) a fragment consisting of amino acid residues 169-183 of human Il-6, (iv) a fragment consisting of amino acid residues 31-45 of human Il-6 and (v) a fragment consisting of amino acid residues 58-72 of human IL-6.

Claims

1-37. -37. (canceled)

138. A nucleic acid or nucleic acids, which nucleic acid or nucleic acids separately or in combination encode for the variable heavy (VH) and the variable light (VL) regions of an antibody or antibody fragment specifically binds human IL-6, wherein said antibody or antibody fragment specifically binds to an epitope on an intact human IL-6 polypeptide, which epitope when ascertained by epitopic mapping using overlapping linear peptide 15-mer fragments which span the full length of the native human IL-6 polypeptide includes one or more residues comprised in each of the following IL-6 fragments (i) a fragment consisting of amino acid residues 37-51 of human Il-6, (ii) a fragment consisting of amino acid residues 70-84 of human Il-6, (iii) a fragment consisting of amino acid residues 169-183 of human Il-6, (iv) a fragment consisting of amino acid residues 31-45 of human Il-6 and (v) a fragment consisting of amino acid residues 58-72 of human IL-6 and which antibody or antibody fragment further competes with an antibody comprising the variable light and heavy regions in SEQ ID NO:

2 and 3 for binding to human IL-6.

139. The nucleic acid or acids of claim 138, wherein the antibody fragment is selected from the group consisting of scFvs, camelbodies, nanobodies, IgNAR (single-chain antibodies derived from sharks) and Fab, Fab′

and F(ab′

)2 fragments.

140. The nucleic acid or acids of claim 138, wherein the encoded antibody or antibody fragment contains a mutation or mutations that eliminate or modify glycosylation.

141. The nucleic acid or acids of claim 138, wherein the nucleic acid or acids further encode human constant domains.

142. The nucleic acid or acids of claim 141, wherein said-human constant domains are IgG1, IgG2, IgG3 or IgG4 constant domains.

143. The nucleic acid or acids of claim 141, wherein said-human constant domains are IgG1 constant domains.

144. The nucleic acid or acids of claim 138, wherein the nucleic acid or nucleic acids further encode an Fc region that has been modified to alter at least one of effector function, half-life, proteolysis, or glycosylation.

145. The nucleic acid or acids of claim 138, wherein the nucleic acid or nucleic acids which encode a humanized antibody or humanized antibody fragment.

146. The nucleic acid or acids of claim 138, wherein the nucleic acid or nucleic acids encode for a human, humanized, single chain or chimeric antibody.

147. A vector containing the nucleic acid or nucleic acids of claim 138.

148. A recombinant cell or virus containing the nucleic acid or nucleic acids of claim 138.

149. A method of making an anti-Il-6 antibody or antibody fragment specifically binds human IL-6, wherein said antibody or antibody fragment that specifically binds to an epitope on an intact human IL-6 polypeptide, which epitope when ascertained by epitopic mapping using overlapping linear peptide 15-mer fragments which span the full length of the native human IL-6 polypeptide includes one or more residues comprised in each of the following IL-6 fragments (i) a fragment consisting of amino acid residues 37-51 of human Il-6, (ii) a fragment consisting of amino acid residues 70-84 of human Il-6, (iii) a fragment consisting of amino acid residues 169-183 of human Il-6, (iv) a fragment consisting of amino acid residues 31-45 of human Il-6 and (v) a fragment consisting of amino acid residues 58-72 of human IL-6 and which antibody or antibody fragment further competes with an antibody comprising the variable light and heavy regions in SEQ ID NO:

2 and 3 for binding to human IL-6, which method comprises;

(i) culturing a cell according to claim 148 under conditions that result in the expression of said antibody or antibody fragment and

(ii) isolating said antibody or antibody fragment from the cell culture.